Anti-dementia drugs. A descriptive study of the prescription pattern in Italy

Introduction: Acetylcholinesterase inhibitors (AChEIs) and memantine are currently the only anti-dementia drugs (ADDs) approved for treating Alzheimer's disease (AD) in Italy. This nationwide study aims to characterize dementia drug utilization in a population > 65 years, during 2018-2020. Methods: Different administrative healthcare databases were queried to collect both aggregate and individual data. Results: ADD consumption remained stable throughout the study period (~ 9 DDD/1000 inhabitants per day). AChEI consumption was over 5 DDD/1000 inhabitants per day. Memantine consumption was nearly 4 DDD/1000 inhabitants per day, representing 40% of ADD consumption. The prevalence of use of memantine represented nearly half of ADD consumption, substantially unchanged over the 3 years. Comparing the AD prevalence with the prevalence of ADDs use, the gap becomes wider as age increases. In 2019, the proportion of private purchases of ADDs was 38%, mostly represented by donepezil and rivastigmine. In 2020, memantine was the only ADD with an increase in consumption (Δ% 19-20, 1.3%). Discussion: To our knowledge, this study represents the first attempt to investigate the ADD prescription pattern in Italy with a Public Health approach. In 2019, the proportion of ADD private purchases point out several issues concerning the reimbursability of ADDs. From a regulatory perspective, ADDs can be reimbursed by the National Health System only to patients diagnosed with AD; therefore, the off-label use of ADDs in patients with mild cognitive impairment may partially explain this phenomenon. The study extends knowledge on the use of ADDs, providing comparisons with studies from other countries that investigate the prescription pattern of ADDs

Generic substitution of antidiabetic drugs in the elderly does not affect adherence

Introduction. The possibility that variation in packaging and pill appearance may reduce adherence is a reason for concern, especially for chronic diseases. The objectives of the study were to quantify the extent of switches between generic antidiabetics and to verify whether switching between different products of the same substance affects adherence. Materials and methods. All elderly residents of the Umbria Region who received at least 2 prescriptions of antidiabetics in 2010 and 2011 were included in the study. Switching was defined as the dispensing of two different products of the same substance in a series of two prescriptions. Single and multiple switchers were identified according to the num-ber of switches during 2011. Switching relevant to the three off-patent substances with generic use ≥ 5% (metformin, gliclazide and repaglinide) was quantified. The effect of switching on adherence, defined as the proportion of days in 2011 covered by prescrip-tions (Medication Possession Ratio, MPR), was estimated.Results. Among the 15 964 patients receiving antidiabetics (14.4% of the elderly popu-lation) 9211 were prescribed at least one of the generic substances. Of these patients, 23.3% experienced a single switch and 15.7% were multiple switchers (61.0% never switched). The proportion of multiple switchers increased with the number of prescrip-tions, reaching 26% among patients with ≥ 11 prescriptions. MPR was 62%, 62% and 72%, respectively among non-switchers, single and multiple switchers.Conclusions. In elderly patients treated with antidiabetics, the substitution between branded and unbranded products (as well as between generics) of the same substance, did not negatively affect adherence

ESTÁGIO SUPERVISIONADO CIÊNCIAS CONTÁBEIS: EMPRESA VILLE INDÚSTRIA DE LICORES LTDA

Este trabalho foi desenvolvido estabelecendo laços entre a teoria e a prática contábil. Foi criada uma indústria de bebidas destiladas, que recebeu o nome fantasia de Ville Indústria de Licores Ltda. A etapa inicial foi a constituição da empresa voltada especificamente à produção de licores com sabores e composições diferentes, sem conservantes químicos. Foram aplicados estudos voltados ao seu processo produtivo, legislação trabalhista e tributária, cálculos de preço de venda, mark-up e ponto de equilíbrio. Na segunda etapa, foi aplicado um sistema contábil a partir de cálculos demonstrativos das operações realizadas pela empresa. Com isso, foi possível efetuar os lançamentos contábeis, a apuração de impostos, a elaboração das demonstrações contábeis e as análises financeiras obtidas dos cálculos de indicadores. Os resultados demonstraram que a Contabilidade tem como essência a teoria executada na prática. Esses meios são fontes de informações gerenciais para uma melhor tomada de decisão do gestor e do investidor. A atividade demonstrou que, apesar da elevada carga tributária da empresa, suas margens são positivas, pois possui uma grande procura do mercado.Palavras chave: Licores. Pesquisas. Princípios contábeis

Antihypertensive drug use during pregnancy: a population based study

Purpose. The study aimed at assessing if the European guideline on the use of antihyper-tensive drugs (AD) in pregnancy are followed in clinical practice. We also evaluated the association between the use of non-recommended drugs and individual characteristics. Methods. This study analyzed a cohort of 86 171 singleton deliveries occurring between 2009-2010 in the Lombardy region, Italy. Women with first prescription of AD during pregnancy were considered as incident users. Methyldopa, labetalol and nifedipine were considered as “recommended drugs”; all other AD were considered as “non-recommend-ed”. Odds Ratio and 95% confidence intervals were estimated.Results. Among the 1009 patients (1.2%) exposed to AD during pregnancy, 675 (66.9%) were incident users. Among the incident users, 31% received non-recommended drugs; this proportion decreased to 18% among women who started treatment in the third tri-mester. Women with at least four concomitant diseases had an elevated risk of receiving non-recommended drugs in pregnancy (OR 2.68; 95% CI 1.10-6.73).Conclusions. Exposure to recommended antihypertensives increased during pregnancy. Nevertheless, a fraction of users that continued or began treatment with non-recom-mended medications was still present. 

Effectiveness of different local actions to control vitamin D prescription in Italy

Introduction. In the last decade, the significant expenditure and consumption increase of vitamin D in Italy led some regions to adopt strategies to improve prescribing appropriateness and contain expenditure. Materials and methods. Using the statistical analysis method of interrupted time series for consumption and expenditure of cholecalciferol, different types of interventions adopted in four Italian regions and their efficacy were evaluated. Results. Molise achieved the best results by adopting a health professionals’ education program in addition to a prescriber-sanction system. Emilia-Romagna also opted for a medical education strategy, but the results were less relevant due to the lack of penalties. Lazio obtained a slowdown in consumption growth by targeting on the utilization of lower-cost per defined daily dose (DDD) packs and adopting a therapeutic plan. Sardinia showed a decrease in expenditure by adopting a target threshold of lower-cost  formulation. Conclusion. The reimbursement of the lowest-cost packs within the National Health Service (NHS) undoubtedly influences spending trend, but it does not solve prescriptive  inappropriateness

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Death in Patients Hospitalised with COVID-19: A Retrospective Italian Cohort Study of 43,000 Patients

Introduction The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. Objective The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. Methods This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. Results Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89-1.06) or ARB (HR 0.98, 95% CI 0.89-1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. Conclusions ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis

Time to Treatment Intensification in Patients Receiving DPP4 Inhibitors Versus Sulfonylureas as the First Add-On to Metformin Monotherapy: A Retrospective Cohort Study

Background: To verify whether, in patients on metformin (MET) monotherapy for type 2 diabetes (T2D), the add-on of a dipeptidyl peptidase inhibitor (DPP4i) compared to a sulfonylurea (SU) can delay the time to the subsequent treatment intensification (TI). Methods: Population-based administrative data banks from four Italian geographic areas were used. Patients aged ≥18 years on MET monotherapy receiving first DPP4i or SU dispensing between 2008 and 2015 (cohort entry) were followed up to the occurrence of TI (insulin dispensing or add-on of a third non-insulin hypoglicemic >180 days after cohort entry), treatment discontinuation, switch, cancer, death, TI occurrence within, end of data availability, end of study period (31 December 2016), whichever came first. Patients on MET + DPP4i were matched 1:1 with those on MET + SU by sex, age, year of cohort entry, and data bank. Hazard Ratio (HR) and 95% confidence intervals (95%CI) were estimated using multivariable Cox regression model including matching variables and potential confounders measured at baseline. Different sensitivity analyses were performed: i) matching at 180 days after cohort entry, ii) intent to treat (ITT) analysis, iii) matching by duration of MET monotherapy, iv) matching by propensity score. Results: The matched study cohort included 10,600 patients. Overall, 763 TI were observed (4.5/100 person-years; mean follow-up = 1.6 years). The primary analysis showed no difference in time to TI between the two groups (HR = 1.02; 95% CI = 0.88–1.19). Sensitivity analyses confirmed this result, except from the ITT analysis (HR = 1.27; 1.13–1.43). Conclusion: The use of a DPP4i rather than a SU as add-on to MET monotherapy was not associated with a delay in treatment intensification

Patterns and trends of utilization of incretin-based medicines between 2008 and 2014 in three Italian geographic areas

Background: The incretin-based medicines GLP1 analogues (GLP1a) and dipeptidyl peptidase-4 inhibitors (DPP4i) are hypoglycaemic agents licensed for the treatment of type 2 diabetes mellitus (T2DM). Although these drugs possess comparable efficacy and low risk of hypoglycaemia, differences in terms of route of administration (subcutaneous versus oral), effect on body weight and gastrointestinal tolerabily can impact their actual use in clinical practice. This study aimed to describe the real-world utilization of incretin-based medicines in the Italian clinical practice. Methods: A multi-database, population-based, descriptive, cohort study was performed using administrative data collected between 2008 and 2014 from three Italian geographic areas. Subjects aged 6518 were selected. New users were defined as those with 651 dispensing of GLP1a or DPP4i during the year of interest and none in the past. Trends of cumulative annual incidence of use in the general adult population were observed. New users of GLP1a or DPP4i were respectively described in terms of demographic characteristics and use of antidiabetic drugs during 1 year before and after the first incretin dispensing. Results: The overall study population included 4,943,952 subjects. A total of 7357 new users of GLP1a and 41,907 of DPP4i were identified during the study period. Incidence of use increased between 2008 (0.2\u2030 for both GLP1a and DPP4i) and 2011 (GLP1a = 0.6\u2030; DPP4i = 2.5\u2030) and slightly decreased thereafter. In 2014, 61% of new GLP1a users received once-daily liraglutide while 52% of new DPP4i users received metformin/DPP4i in fixed-dose. The percentage of new DPP4i users older than 65 years of age increased from 30.9 to 62.6% during the study period. Around 12% of new users had not received any antidiabetic before starting an incretin. Conclusions: During the study period, DPP4i rapidly became the most prescribed incretin-based medicine, particularly among older new user. The choice of the specific incretin-based medicine at first prescription appeared to be directed towards those with higher convenience of use (e.g. oral DPP4i rather than subcutaneous GLP1a, once-daily liraglutide rather than twice-daily exenatide). The non-negligibile use of incretin-based medicines as first-line pharmacotherapy for T2DM warrants further effectiveness and safety evaluations to better define their place in therapy

Estudo de motor universal com núcleos obtidos pelos processos da metalurgia do pó para utilização em furadeiras manuais

Este trabalho teve por objetivo o estudo de ligas sinterizadas a partir de Fe puro, FeP, FeSi e FeNi obtidas a partir dos processos da Metalurgia do Pó para sua aplicação nos núcleos do rotor e estator de um motor universal, tendo como finalidade sua utilização em uma máquina furadeira manual. A pesquisa compreendeu a obtenção de curvas de histerese destas ligas, ensaios para avaliação de perdas elétricas e simulação em software de elementos finitos para obtenção de fluxo de entreferro e conjugado eletromagnético (torque). Os estudos teóricos foram realizados em um motor universal de topologia convencional e as simulações foram realizadas de forma a comparar este motor com os de núcleos fabricados a partir de chapas de aço laminadas